Schizophrenia is among the most disabling illnesses of adults in the world. With illness onset typically occurring in young adulthood, individuals with schizophrenia often struggle to establish and maintain social and work roles in the community. In recognition of the profound disability associated with schizophrenia, the Veteran's Health Administration has prioritized provision of mental health care services to adults with severe and persistent mental illnesses. The President's New Freedom Commission called for the development of mental health care services that focus on "increasing consumer's ability to successfully cope with life challenges, on facilitating recovery, and on building resilience." The proposed intervention study is designed to enhance cognition and psychosocial functioning in patients. The cognitive dysfunction associated with schizophrenia has been found to be one of the strongest predictors of how well patients do in the community. Cognitive remediation is a computer-based intervention that was developed to restore cognitive functioning in patients with brain injury. This intervention has been adapted successfully for use with patients with schizophrenia. The proposed treatment study draws upon recent research findings which suggest both that working memory is a critical, potentially performance-limiting, cognitive deficit in schizophrenia and that with intervention, clinically significant change can occur within this domain. The primary aim of the proposed study is to test the efficacy of a novel cognitive remediation intervention that targets working memory-related functions. To accomplish this goal, 80 volunteer patients with schizophrenia will be enrolled and randomized to either a cognitive remediation condition that targets working memory or a computer skills training intervention that teaches computer applications. In both conditions participants will receive computer training three times a week for 4 months. We hypothesize that patients who receive the cognitive remediation intervention will demonstrate significantly greater change on neuropsychological measures of working memory and executive abilities than patients who receive the computer skills course. In addition, we hypothesize that the intervention- induced cognitive change will be associated with concurrent improvements in functional capacity and psychosocial functioning in the community. A second study goal is to examine the stability of the intervention- induced changes in cognition. Cognition and psychosocial functioning will be reassessed 4 and 8 months after treatment termination to examine the stability of treatment effects and to assess whether a less intense maintenance training (once a week sessions) provides any additional benefit to participants. Lastly, this study will examine in an exploratory manner whether there are individual differences in treatment response. The Val158Met polymorphism of the COMT gene has been found to be associated with working memory and prefrontal dysfunction in schizophrenia. The proposed study will test whether the COMT polymorphism is predictive of response to cognitive remediation. PUBLIC HEALTH RELEVANCE: Schizophrenia is often diagnosed in young adulthood and marked by a decline in psychosocial functioning. The illness emerges at a stage in life in which many men and women have elected to serve in the military. Consequently, schizophrenia has been, and is likely to continue to be, a disabling illness prevalent among veterans. In recognition of veteran's mental health care needs, the Veterans Health Administration's (VHA) Mental Health Strategic Plan prioritized services for veterans with serious and persistent mental illness. The proposed treatment study is designed to test the efficacy of a cognitive remediation intervention developed specifically to enhance cognition, skillfulness with everyday activities, and rate of participation in the community in individuals with schizophrenia. If cognitive remediation of working memory is found to enhance cognition and psychosocial functioning as predicted, this study would produce empirical support for a non-invasive psychosocial intervention that promotes recovery in patients with schizophrenia. Given that the vast majority of patients with schizophrenia are cognitively impaired, there is significant need for interventions that target this aspect of the illness. The functional disability associated with the cognitive impairment in this population is one of the most distressing aspects of the illness to both patients and family members, and improvement in psychosocial functioning is frequently a goal that both patients and family members are motivated to work toward. Development of a cognitively enhancing intervention would fill a gap in the current mental health services offered to this population. Development of such an intervention is also consistent with the President's New Freedom Commission's mission to provide mental health care services that focus on "increasing consumers'ability to successfully cope with life challenges, on facilitating recovery, and on building resilience." If the study hypotheses are supported, the proposed treatment study would provide empirical support for the efficacy of a non-invasive intervention that would increase patients'capacity to learn skills of daily living and to function in the community. This intervention could be immediately available for dissemination within the VA system, and would give treatment providers an evidence-based intervention to offer patients to assist them in working toward their recovery goals.